Abnormally fast heart rates are called tachycardias. When the tachycardia occurs in the top chambers of the heart (the atria), this is termed atrial tachycardia. When it occurs in the bottom chambers (the ventricles), this is termed ventricular tachycardia. These rhythms can be highly symptomatic in the case of atrial tachycardia or can be life-threatening in the case of ventricular tachycardia.
These rhythms are often due to diseased or dead myocardial tissue, which may form a scar. Under normal conditions, all myocardial cells conduct electrical activity. When a myocardial cell depolarizes, the ionic membrane potential changes; which as a result, can cause its neighbor myocardial cell to depolarize, and so on. Therefore, depolarizing cells result in a self-propagating mechanism, whereby depolarizing wavefronts travel through myocardial tissue. In certain settings, a propagating wavefront may travel around non-conducting tissue. If each cell along this reentrant pathway has enough time to repolarize the cell's membrane potential, the resulting wavefront can then get caught in a perpetual loop where the electrical signal in the myocardial tissue circles around a fixed point or central scar. The action potentials will continually propagate around the non-conducting tissue (such as a prior myocardial infarction) at a rate considerably faster than the heart's intrinsic rate. The reentrant circuit can be thought of as a conduction wavefront propagating along a tissue mass of approximately circular geometry.
Initially, these dangerous rhythms were treated with an external shock (defibrillation) that resets the myocardial tissue to regain normal sinus rhythm. As implanted devices became more complex, pacing modalities were created to attempt to pace-terminate the tachycardia. This is termed anti-tachycardia pacing (ATP). When ATP strategies fail, the device may then proceed with painful how powered shocks; which usually are very painful to the patient. ATP, on the other hand, is usually painless.
The rate at which myocardial tissue can allow a propagating wavefront to conduct through it has a limit. Once depolarized, the tissue must repolarize in order to conduct another propagating wavefront. If a wavefront approaches myocardial tissue which has not repolarized the tissue cannot conduct the wavefront and the electrical signal will terminate. Tissue that has not yet repolarized and cannot conduct an electrical signal is termed refractory.
To terminate an arrhythmic circuit, a pacing stimulus is provided at a time and location such that the resulting wave propagation fails to conduct down the pathway of the reentrant circuit. When pacing faster than the reentry tachycardia, the paced stimulation wavefront proceeds toward the arrhythmic circuit. This wavefront can approach both sides of the reentrant circuit (see FIG. 4 for clarity); such that the wavefront will collide with the wavefront leaving the reentrant circuit (termed the ‘exit’ site). With more pacing, the paced wavefront will reach the native tachycardia prior to the reentrant wavefront; resulting in an earlier depolarization of the reentrant circuit. With substantially continuous pacing, we can reach “entrainment,” whereby the wavefront traveling towards the exit site, will collide with the wavefront from the prior wavefront within the arrhythmic circuit (in the retrograde direction). The paced wavefront will also proceed towards the entrance site of the reentrant tachycardia and proceed down the path of the arrhythmic circuit in the orthograde direction. If the pacing rate is accelerated, this orthodromic wavefront may reach a part of the arrhythmia circuit before it has repolarized and is therefore refractory. If this occurs, the wavefront may terminate and the arrhythmia will end. Accordingly, the probability of anti-tachycardia pacing (ATP) succeeding in terminating a tachycardia is related to the ability of the pacing stimulation wavefront to arrive at the location of the reentrant circuit in such a manner that the propagating signal in the reentrant circuit is modified, is unable to perpetuate the propagating signal, and the tachycardia is terminated.
Numerous different pacing modalities and algorithms have been created for the termination of tachycardia. These algorithms have been created for both atrial and ventricular tachycardias. These algorithms are programmed into implanted devices such as a pacemaker or implantable cardioverter-defibrillators (ICDs). These devices may deliver a high powered electrical shock which attempts to reset all cells involved in the reentrant tachycardia in order to terminate the tachycardia. These shocks are often painful and can cause harm to myocardial cells. Alternatively, the devices may deliver anti-tachycardia pacing (ATP), whereby paced wavefronts reach critical aspects of the reentrant circuit in such a manner that the tachycardia terminates. ATP is usually painless and therefore has advantages over high-powered cardioversions.
ATP is not always successful at terminating the tachycardia. In this circumstance, the ATP is repeated at the same or different pacing algorithm in attempts to terminate the arrhythmic into a normal sinus rhythm. If ATP is unsuccessful, the patient may require high voltage cardioversion. ATP is unsuccessful in approximately 10-40% of ATP attempts. In addition, ATP sometimes accelerates the rhythm to a faster rate or may degenerate the rhythm into ventricular fibrillation, which is a chaotic rhythm that is not capable of sustaining life. Furthermore, the longer the patient is in ventricular tachycardia, the more likely the patient is to pass out (syncope) which is dangerous.
Thus, improved methods for increasing the success rate of ATP and for decreasing the time in tachyarrhythmia, which will reduce the need for painful ICD shocks, are needed.
ATP often functions by entraining the tachycardia. Entraining is a process whereby paced beats (by a pacemaker lead, for example) accelerates the tachycardia. One or more stimulations are provided at a rate slightly faster than the tachycardia, such that the paced wavefronts enter and accelerate the tachycardia. The first paced stimulation that advances the reentrant tachycardia resets the tachycardia. The next pacing stimulation typically advances the tachycardia to the paced cycle length. Since myocardial tissue properties often change in response to shorter cycle lengths, several resetting stimulations may be needed to completely advance the tachycardia to the pacing cycle length. Each paced beat then ‘resets’ the tachycardia to the faster rate, termed entrainment. Ideally, the faster rate is too fast for the arrhythmic circuit, such that the tissue has not had enough time to repolarize. In this case, the wavefront terminates, and the patient returns to sinus rhythm.
Entrainment involves identifying a specific response of a reentrant arrhythmia to external pacing, including: (1) beat to beat interaction between the paced and tachycardia wavefront; (2) activation of all the tissue in the chamber where the circuit is located; and (3) persistence of the tachycardia after pacing, if the tachyarrhythmia does not self-terminate. If the self-sustaining tachyarrhythmia of the heart is thought of as an electrical circuit running in a circle, one can “entrain” that circuit by pacing slightly faster than the circuit was running on its own. This is known as resetting the circuit, as the tissue in the circuit will now be excited at the new, faster, paced rate, as compared to the pace at which the circuit ran on its own before entrainment. If the circuit can propagate at the faster rate, when this re-setting is stopped, the pacing catheter electrode in the heart can then measure the time required for the last paced beat to create a wavefront, enter the arrhythmic circuit, propagate around a portion of the arrhythmic circuit, and then exit to the same electrode or catheter. This time is termed the post-pacing interval (PPI). The post-pacing interval has long been used as an indication of the proximity of the pacing site to the reentry circuit. (Stevenson, Khan et al. 1993) (Waldo 1997).
The efficacy of the delivery of anti-tachycardia pacing (ATP) through the right ventricular implantable cardioverter defibrillator (ICD) lead to terminate life-threatening fast ventricular tachycardia (FVT) was first published in 2001 by Wathen et al. In this study, the authors revealed that ATP could prevent ICD shock delivery in 3 of 4 episodes. Over the following years, ATP has become a valuable option to treat most VT episodes. Large-scale studies, including PainFree Rx II, EMPIRIC, PREPARE, or ATPonFastVT, have demonstrated the efficacy and safety of this approach. Moreover, delivering ATP instead of defibrillation has dramatically reduced the number of painful ICD shocks.
Typically, the ATP algorithm depends on the type (atrial versus ventricular) and rate of the tachycardia. For example, most device makers make a distinction between ventricular tachycardia (VT), fast ventricular tachycardia (FVT), and ventricular fibrillation (VF) based on the rate of the tachycardia. The tachycardia rate can be described in terms of beats per minute (BPM) or can be thought of as the time between heart beats (termed the RR interval). This time is also termed the tachycardia cycle length (TCL), and is often given in milliseconds, 60,000 divided by the heart rate provides the cycle length in milliseconds (ms). For example, a tachycardia of 200 BPM has a tachycardia cycle length of 300 ms.
ATP can be a pacing train of a certain cycle length (burst pacing) or can shorten the cycle length with each additional paced beat (often termed ramp pacing). Ramp therapy consists of a decremental drive of a programmable number of pulses, starting at a rate proportional to the current tachycardial cycle length (TCL).
The current algorithms of ATP are well known and easily accessible. One example (described below) is by implantable device maker Medtronic, although all device makers have created similar pacing algorithms.
In Medtronic's PainFREE Rx II Trial, the first therapy in the FVT zone (188-250 BPM) was 2 ATP sequences (8-pulse burst pacing train at 88% of the FVT cycle length). If the first ATP sequence was unsuccessful, the second sequence was delivered at 88% of the FVT cycle length minus 10 ms. ATP therapies were delivered at maximum voltage and pulse duration. Programming of subsequent FVT therapies was left to the investigators' discretion and usually involved ICD shocks.
A recent study by Martins et al published in Eurospace (2012) performed a study involving the major ICD device makers: Biotronik, Boston Scientific, Medtronic, St Jude Medical and Sorin Group companies. In this study, the ventricular ATP algorithm was as follows: Implantable cardioverter/defibrillators were programmed to deliver 10 ATP attempts for FVT cycle lengths (CLs) of 250-300 ms (200-240 BPM) before shock delivery (5 bursts, then 5 ramps; 8-10 extrastimuli at 81-88% FVT CL; minimal pacing CL 180 ms). A total of 1839 FVTs, 1713 of which were ATP-terminated (unadjusted efficacy ¼ 93.1%, adjusted ¼ 81.7%). Furthermore, over 20% of the patient experienced. ATP that required more than two episodes of ATP.
Thus, there is room to improve the current ATP algorithms to reduce the time spent in tachycardia and prevent ICD shock.
The most advanced pacemakers feature atrial preventive pacing and atrial anti-tachycardia pacing (DDDRP), which may reduce atrial fibrillation occurrence and duration. The device automatically delivers ATP therapies when an episode is classified as atrial tachycardia and lasts longer than a programmable ‘time to first therapy’ (often 1 min). Often, ramp is programmed in order to deliver three series of ten sequences each, so that each patient could receive up to thirty termination attempts. Each series begins with a train of ten pulses. The first pulse of each of the three series is delivered at 91, 84, and 81% of the underlying atrial tachycardia cycle length (ATCL), respectively. In each series, subsequent pulses were delivered with a decrement in pacing coupling interval of 10 ms each. If a previous train fails to terminate AT, an additional stimulus is added to the next train.
Burst+ therapy uses a drive of a programmable number of atrial pulses, the rate of which is proportional to the current ATCL, followed by up to two extrastimuli. Burst+ is programmed in order to deliver three series of ten sequences each; each sequence is made up of fifteen pulses followed by two extrastimuli. As in the Ramp programming, each patient can receive up to thirty termination attempts. The first scan of each series is released at 84% of the underlying ATCL. The first extrastimulus is delivered at 81% of the underlying ATCL; the second extrastimulus was delivered with an interval reduced by 20 ms. In the event of failure, the ATP train coupling interval was decreased by 10 ms for each subsequent scan.
For both therapies, the minimal pacing interval (MPI) was 150 ms, so that pulses programmed at a shorter pacing interval than the MPI were delivered at the MPI value. Atrial ATP was recently found to significantly reduce the progression of atrial tachycardia to permanent atrial fibrillation (61% relative risk reduction) over a 2 year follow-up.
Previous methods use similar strategies for all tachycardias. These strategies use a burst or a ramp strategy with variable number of beats. If this ATP attempt fails, another burst or ramp is delivered at shorter intervals (faster rates). We have devised unique pacing algorithms based on novel concepts to improve the ability of a device to terminate a tachycardia.